April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Stem Cells Play a Key Role in the Formation of the Human Choroidal Vasculature and Mural Cells
Author Affiliations & Notes
  • A. Korlimbinis
    Bosch Institute, University of Sydney, Sydney, Australia
  • L. Baxter
    Bosch Institute, University of Sydney, Sydney, Australia
  • S. Yun
    Bosch Institute, University of Sydney, Sydney, Australia
  • J. Dahlstrom
    Pathology Department, Australian National University, Canberra, Australia
  • M. Koina
    Pathology Department, Australian National University, Canberra, Australia
  • R.-A. Sterling
    Bosch Institute, University of Sydney, Sydney, Australia
  • E. Bean
    Pathology Department, Australian National University, Canberra, Australia
  • S. Hughes
    Bosch Institute, University of Sydney, Sydney, Australia
  • T. Chan-Ling
    Bosch Institute, University of Sydney, Sydney, Australia
  • Footnotes
    Commercial Relationships  A. Korlimbinis, None; L. Baxter, None; S. Yun, None; J. Dahlstrom, None; M. Koina, None; R.-A. Sterling, None; E. Bean, None; S. Hughes, None; T. Chan-Ling, None.
  • Footnotes
    Support  National Health & Medical Research Council of Australia (#464859, #571100), Baxter Charitable Foundation, Macular Vision Support Society, Rebecca L. Cooper Medical Research Foundation
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4939. doi:
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      A. Korlimbinis, L. Baxter, S. Yun, J. Dahlstrom, M. Koina, R.-A. Sterling, E. Bean, S. Hughes, T. Chan-Ling; Stem Cells Play a Key Role in the Formation of the Human Choroidal Vasculature and Mural Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4939.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To undertake the first complete study of human choroidal vascular formation & determine the role played by stem cells.

Methods: : Human foetal eyes aged 8-40 weeks gestation (WG) were examined. Choroidal & retinal wholemounts & histological sections were examined using antibodies for stem & precursor cell populations: Vimentin, CD14, CD34, CD39 & SMA; the vasculature: CD39, CD34, CD31 & Factor VIII; & mural cells: SMA, Desmin, NG2, Calponin & Caldesmon. Endothelial proliferation was examined by double-labelling with BrdU & CD34. TEM and H & E histology was also undertaken.

Results: : Vimentin+ mesenchymal precursor cells were evident in the region of the incipient choroid at 9 WG, & down regulation of Vimentin was evident with maturation. CD14+ vascular precursor cells (VPCs) were evident in the choroidal stroma throughout foetal life. CD39+/CD34+ VPCs were evident within the choroidal stroma from 10 WG, interspersed amongst CD39+ solid vascular chords in the central one-third of the choroid surrounding the optic nerve head. SMA+ mural precursor cells (MPCs) were scattered & isolated over the primordial vascular tree at 12WG. Non vascular-associated SMA+/CD34+/--/ NG2+/desmin- presumed MPCs were associated with immature choroidal blood vessels at 12, 18 & 20 WG. Calponin & caldesmon were expressed only on the large vessels. Remarkably, pericytes were absent on human choroidal vessels.

Conclusions: : We conclude that formation of the human choroid takes place via transformation from Vimentin+ mesenchymal precursor cells to CD14+/CD39+/SMA+ precursor cells representing the monocytic vascular and mural cell lineages respectively. Vasculogenesis plays a greater role in formation of human choroid than previously reported but angiogenesis also contribute to vascular density in the formation of the human choroid. We have shown that CD44+ stem cells give rise to SMA+ smooth muscle cells & CD39+ vascular endothelial cells in the human choroid. Moreover, there is a marked difference in pericyte ensheathment between choroidal & retinal vessels, underlying the marked difference in auto-regulatory ability reported between the two vascular plexii.

Keywords: retinal development • choroid: neovascularization • age-related macular degeneration 
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